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Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier

BACKGROUND: Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key...

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Autores principales: Griffin, Jarred M., Kho, Dan, Graham, E. Scott, Nicholson, Louise F. B., O’Carroll, Simon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911157/
https://www.ncbi.nlm.nih.gov/pubmed/27309956
http://dx.doi.org/10.1371/journal.pone.0157483
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author Griffin, Jarred M.
Kho, Dan
Graham, E. Scott
Nicholson, Louise F. B.
O’Carroll, Simon J.
author_facet Griffin, Jarred M.
Kho, Dan
Graham, E. Scott
Nicholson, Louise F. B.
O’Carroll, Simon J.
author_sort Griffin, Jarred M.
collection PubMed
description BACKGROUND: Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. AIMS: To determine if fAβ is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fAβ. METHODS: Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary β-amyloid(1–42) (fAβ(1–42)) alone and in combination with statins. RESULTS: fAβ(1–42) induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. CONCLUSIONS: We conclude that fAβ(1–42) has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects.
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spelling pubmed-49111572016-07-06 Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier Griffin, Jarred M. Kho, Dan Graham, E. Scott Nicholson, Louise F. B. O’Carroll, Simon J. PLoS One Research Article BACKGROUND: Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. AIMS: To determine if fAβ is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fAβ. METHODS: Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary β-amyloid(1–42) (fAβ(1–42)) alone and in combination with statins. RESULTS: fAβ(1–42) induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. CONCLUSIONS: We conclude that fAβ(1–42) has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects. Public Library of Science 2016-06-16 /pmc/articles/PMC4911157/ /pubmed/27309956 http://dx.doi.org/10.1371/journal.pone.0157483 Text en © 2016 Griffin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Griffin, Jarred M.
Kho, Dan
Graham, E. Scott
Nicholson, Louise F. B.
O’Carroll, Simon J.
Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title_full Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title_fullStr Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title_full_unstemmed Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title_short Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier
title_sort statins inhibit fibrillary β-amyloid induced inflammation in a model of the human blood brain barrier
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911157/
https://www.ncbi.nlm.nih.gov/pubmed/27309956
http://dx.doi.org/10.1371/journal.pone.0157483
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